tbuckley/cabot-search huggingface dataset:
Letter to the Editor: Variability in serum creatinine is associated with waitlist and post–liver transplant mortality in patients with cirrhosis
Authors: Abdullah Ahmed, Muhammad W. Arshad, Hamza Ibrahim
Journal: Hepatology (2023)

To the editor, It was a great pleasure to read the article "Variability in serum creatinine is associated with waitlist and post–liver transplant mortality in patients with cirrhosis" by Cullaro et al1 in which the authors determined the impact of variation in clinical function of kidney on pre-liver transplantation (LT) and post-LT outcomes. The article was very well put, and the authors did a great job, but we have a few points in mind that we would like to mention. First, authors defined acute kidney injury (AKI) solely on the basis of variability in serum creatinine. While this is a reasonable parameter to define AKI, some other studies have used other specific biomarkers to assess it. For example, the study conducted by Singal et al2 showed that biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and FABBP-2 can diagnose AKI earlier. These biomarkers are also very useful in differentiating acute tubular necrosis in AKI from hepatorenal syndrome. Second, no account of renal recovery after LT has been given. The same aforementioned study2 indicates that uromodulin (UMOD) is a key biomarker in predicting renal recovery after LT. Similarly elevated osteopontin (OPN) and TIMP-1, age below 57 years, and absence of diabetes are important renal recovery predictors. Third, the authors mentioned that they assessed chronic kidney disease as an estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥90 days. However, they did not mention the method by which they calculated estimated glomerular filtration rate. In this study,3 estimated glomerular filtration rate was calculated using both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and MDRD-4 formulas. Fourth, the authors mentioned that the limited UNOS database may not allow them to investigate and have a richer analysis on the topic due to limited or absent information regarding comorbidities like diabetes mellitus and degree of ascites. However, they also did not mention anything about the dose of loop and potassium-sparing diuretics or sodium-restricted diet in patients with kidney injury at the time of study enrollment as indicated in the study.3 These parameters can have notable impact on the result of this study. Finally, I would like to commend the authors for their excellent contribution to the field of hepatology. Their article provides a comprehensive overview of the current state of knowledge regarding the relationship between kidney function and pre/post–liver transplant outcomes in a patient. I believe that this article will serve as a valuable resource for clinicians and researchers working in this area.
Reply: Variability in serum creatinine is associated with waitlist and post–liver transplant mortality in patients with cirrhosis
Authors: Giuseppe Cullaro
Journal: Hepatology (2023)

We appreciate the thoughtful commentary. We believe the writers raise several important points: How to define acute kidney injury (AKI)? We agree in principle that biomarkers of injury (eg, neutrophil gelatinase-associated lipocalin [NGAL]) and repair (eg, TIMP-2) can serve as more sensitive and specific metrics of AKI in a population where creatinine is intrinsically less accurate.1–3 Currently, there are no approved and readily available kidney biomarkers outside clinical research. Given this limitation, this strengthens our findings that the variation in sCr can serve as an implementable, readily available metric. What are the metrics of AKI reversal? This is a key outcome before and after liver transplantation. We believe that the drivers of AKI reversal are dictated by the kidney reserve and the severity of the injury—with many of the postulated biomarkers being linked to each of these pathways.4–7 We hypothesize that the variability in serum creatinine may capture both of these pathways—those with less reserve are more likely to have an episode of AKI, and those with a more severe episode of AKI are more likely to have greater variability.8 How to define chronic kidney disease? We apologize for not being transparent in our methods—for this analysis, we used the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI with serum creatinine). How to best study kidney dysfunction among patients with cirrhosis? Kidney dysfunction among cirrhosis patients is complex—we agree that underlying clinical factors may drive greater variation in serum creatinine, with a degree of ascites, hemodynamics, and frailty all likely being major contributors.1 We have an ongoing cohort to better adjust for each of these dimensions. That said, we believe the variation in sCr can be a readily available metric to capture the risk of adverse kidney-related outcomes before and after liver transplantation. We thank the authors for their thoughtful comments and Hepatology for the opportunity to expand on our work.
Changes in local tissue microenvironment in response to subcutaneous long-acting delivery of tenofovir alafenamide in rats and non-human primates
Authors: Fernanda P. Pons-Faudoa, Nicola Di Trani, Simone Capuani, Nathanael Hernandez, Anthony M. Wood, Bharti Nehete, Jean Niles, Kathryn A. Shelton, Sarah Kezar, Lane R. Bushman, Corrine Ying Xuan Chua, Michael M. Ittmann, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Joan E. Nichols, Alessandro Grattoni
Journal: Journal of Controlled Release (2023)

Several implantable long-acting (LA) delivery systems have been developed for sustained subcutaneous administration of tenofovir alafenamide (TAF), a potent and effective nucleotide reverse transcriptase inhibitor used for HIV pre-exposure prophylaxis (PrEP). LA platforms aim to address the lack of adherence to oral regimens, which has impaired PrEP efficacy. Despite extensive investigations in this field, tissue response to sustained subcutaneous TAF delivery remains to be elucidated as contrasting preclinical results have been reported in the literature. To this end, here we studied the local foreign body response (FBR) to sustained subdermal delivery of three forms of TAF, namely TAF free base (TAFfb), TAF fumarate salt (TAFfs), and TAFfb with urocanic acid (TAF-UA). Sustained constant drug release was achieved via titanium–silicon carbide nanofluidic implants previously shown to be bioinert. The analysis was conducted in both Sprague-Dawley (SD) rats and rhesus macaques over 1.5 and 3 months, respectively. While visual observation did not reveal abnormal adverse tissue reaction at the implantation site, histopathology and Imaging Mass Cytometry (IMC) analyses exposed a local chronic inflammatory response to TAF. In rats, UA mitigated foreign body response to TAF in a concentration-dependent manner. This was not observed in macaques where TAFfb was better tolerated than TAFfs and TAF-UA. Notably, the level of FBR was tightly correlated with local TAF tissue concentration. Further, regardless of the degree of FBR, the fibrotic capsule (FC) surrounding the implants did not interfere with drug diffusion and systemic delivery, as evidenced by TAF PK results and fluorescence recovery after photobleaching (FRAP).
[<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group
Authors: Karin Oechsle, Michael Hartmann, Winfried Brenner, Stephan Venz, Lothar Weissbach, Christiane Franzius, Sabine Kliesch, Stephan Mueller, Susanne Krege, Ruediger Heicappell, Roland Bares, Carsten Bokemeyer, Maike de Wit
Journal: Journal of Clinical Oncology (2008)

Purpose In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM). Patients and Methods A total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT. Results Prediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET. Conclusion The presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.
Absence of Cardiac Toxicity of Zidovudine in Infants
Authors: Steven E. Lipshultz, Kirk A. Easley, E. John Orav, Samuel Kaplan, Thomas J. Starc, J. Timothy Bricker, Wyman W. Lai, Douglas S. Moodie, George Sopko, Kenneth McIntosh, Steven D. Colan
Journal: New England Journal of Medicine (2000)

Some evidence suggests that perinatal exposure to zidovudine may cause cardiac abnormalities in infants. We prospectively studied left ventricular structure and function in infants born to mothers infected with the human immunodeficiency virus (HIV) in order to determine whether there was evidence of zidovudine cardiac toxicity after perinatal exposure.
Stent Placement Compared with Balloon Angioplasty for Obstructed Coronary Bypass Grafts
Authors: Michael P. Savage, John S. Douglas, David L. Fischman, Carl J. Pepine, Spencer B. King, Jeffrey A. Werner, Steven R. Bailey, Paul A. Overlie, Sarah H. Fenton, Jeffrey A. Brinker, Martin B. Leon, Sheldon Goldberg, Richard Heuser, Richard Smalling, Robert D. Safian, Michael Cleman, Maurice Buchbinder, David Snead, Randal C. Rake, Sharon Gebhardt
Journal: New England Journal of Medicine (1997)

Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts.
Gender Differences in the Prescribing of Antipsychotic Drugs
Authors: Mary V. Seeman
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The aim of this article is to offer recommendations and rationale for gender-specific antipsychotic treatment. METHOD: The author summarizes reviews of recent literature in psychiatric clinical trials, pharmacology, drug safety, toxicology, obstetrics and gynecology, and pediatrics. RESULTS: The pharmacokinetics and pharmacodynamics of antipsychotic drugs differ in women and men and are influenced by gender-specific factors such as body build, diet, smoking, concurrent medication, exercise, substance use, and hormonal transitions. In general, and for some drugs in particular, women require lower doses in order to stay well. Because preliminary drug testing is not done in pregnant women, the issue of effective dosing during pregnancy is unstudied, and safety for fetuses and nursing infants may not become evident until a drug is widely used. Specific adverse effects on issues crucial to women (e.g., parenting) have not been well studied, but some side effects, such as weight gain, passivity, hypotension, and hyperprolactinemia, are reported to be particularly problematic for women. Some serious side effects are more often seen among women than among men. CONCLUSIONS: Optimal maintenance regimens of antipsychotics for women and men are not the same.
A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn–1Mg porous scaffolds as biodegradable bone implants
Authors: Zhenbao Zhang, Aobo Liu, Jiadong Fan, Menglin Wang, Jiabao Dai, Xiang Jin, Huanze Deng, Xuan Wang, Yijie Liang, Haixia Li, Yantao Zhao, Peng Wen, Yanfeng Li
Journal: Bioactive Materials (2023)

Zinc (Zn) alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions, having a great application potential for repairing bone defect. In this work, a hydroxyapatite (HA)/polydopamine (PDA) composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion, and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin. The microstructure, degradation behavior, biocompatibility, antibacterial performance and osteogenic activities were systematically investigated. Compared with as-built Zn-1Mg scaffolds, the rapid increase of Zn2+, which resulted to the deteriorated cell viability and osteogenic differentiation, was inhibited due to the physical barrier of the composite coating. In vitro cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance. Significantly improved osteogenic and antibacterial functions were also observed according to in vivo implantation in the lateral femoral condyle of rats. The design, influence and mechanism of the composite coating were discussed accordingly. It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.
Multiphasic scaffolds for the repair of osteochondral defects: Outcomes of preclinical studies
Authors: Rouyan Chen, Jasmine Sarah Pye, Jiarong Li, Christopher B. Little, Jiao Jiao Li
Journal: Bioactive Materials (2023)

Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.
Association of distinct microbial signatures with premalignant colorectal adenomas
Authors: Jonathan Wei Jie Lee, Damian R. Plichta, Shreya Asher, Marisa Delsignore, Tiffany Jeong, Jessica McGoldrick, Kyle Staller, Hamed Khalili, Ramnik J. Xavier, Daniel C. Chung
Journal: Cell Host & Microbe (2023)
Fusobacterium nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer
Authors: Shan-Shan Jiang, Yi-Le Xie, Xiu-Ying Xiao, Zi-Ran Kang, Xiao-Lin Lin, Lu Zhang, Chu-Shu Li, Yun Qian, Ping-Ping Xu, Xiao-Xu Leng, Li-Wei Wang, Shui-Ping Tu, Ming Zhong, Gang Zhao, Jin-Xian Chen, Zheng Wang, Qiang Liu, Jie Hong, Hao-Yan Chen, Ying-Xuan Chen, Jing-Yuan Fang
Journal: Cell Host & Microbe (2023)
Near‐Infrared Emissive Cascaded Artificial Light‐Harvesting System with Enhanced Antibacterial Efficiency
Authors: Maowen Chen, Zhenni Lu, Man Li, Bei Jiang, Senkun Liu, Yinuo Li, Bangrui Zhang, Xianying Li, Tao Yi, Dengqing Zhang
Journal: Advanced Healthcare Materials (2023)

Combination of platinum(II) metallacycles and photodynamic inactivation presents a promising antibacterial strategy. Herein, a cascaded artificial light-capturing system is developed in which an aggregation-induced emission-active platinum(II) metallacycle (PtTPEM) is utilized as the antenna, sulforhodamine 101 (SR101) as a key conveyor, and the near-infrared emissive photosensitizer Chlorin-e6 (Ce6) as the final energy acceptor. The well-dispersed Ce6 in the proximity of energy donors not only avoids self-quenching in the physiological environment but also contributes to energy transfer from donor to acceptor, thereby significantly improving the 1 O2 generation ability of the light-harvesting system under white light irradiation. By integrating the platinum(II) metallacycle and 1 O2 , a more efficient synergistic antibacterial effect is achieved at low concentrations, along with a significant decrease in dark toxicity caused by PtTPEM.
Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal
Authors: Leslie W. Young, Songthip T. Ounpraseuth, Stephanie L. Merhar, Zhuopei Hu, Alan E. Simon, Andrew A. Bremer, Jeannette Y. Lee, Abhik Das, Margaret M. Crawford, Rachel G. Greenberg, P. Brian Smith, Brenda B. Poindexter, Rosemary D. Higgins, Michele C. Walsh, Ward Rice, David A. Paul, Jessie R. Maxwell, Sucheta Telang, Camille M. Fung, Tanner Wright, Anne Marie Reynolds, Devon W. Hahn, Julie Ross, Jennifer M. McAllister, Moira Crowley, Sophie K. Shaikh, Karen M. Puopolo, Lori Christ, Jaime Brown, Julie Riccio, Kara Wong Ramsey, None Akshatha, Erica F. Braswell, Lauren Tucker, Karen R. McAlmon, Krishna Dummula, Julie Weiner, Jessica R. White, Meghan P. Howell, Sarah Newman, Jessica N. Snowden, Lori A. Devlin
Journal: New England Journal of Medicine (2023)

Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown.In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death.A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups.As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).
Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis
Authors: Fasiha Kanwal, Saira Khaderi, Amit G. Singal, Jorge A. Marrero, Sumeet K. Asrani, Christopher I. Amos, Aaron P. Thrift, Jennifer R. Kramer, Xian Yu, Yumei Cao, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B. El-Serag
Journal: Clinical Gastroenterology and Hepatology (2023)
Caloric restriction remodels the hepatic chromatin landscape and bile acid metabolism by modulating the gut microbiota
Authors: Yun Fan, Hong Qian, Meijia Zhang, Chengzhe Tao, Zhi Li, Wenkai Yan, Yuna Huang, Yan Zhang, Qiaoqiao Xu, Xinru Wang, Paul A. Wade, Yankai Xia, Yufeng Qin, Chuncheng Lu
Journal: Genome biology (2023)

Abstract Background Caloric restriction (CR) has been known to promote health by reprogramming metabolism, yet little is known about how the epigenome and microbiome respond during metabolic adaptation to CR. Results We investigate chromatin modifications, gene expression, as well as alterations in microbiota in a CR mouse model. Collectively, short-term CR leads to altered gut microbial diversity and bile acid metabolism, improving energy expenditure. CR remodels the hepatic enhancer landscape at genomic loci that are enriched for binding sites for signal-responsive transcription factors, including HNF4α. These alterations reflect a dramatic reprogramming of the liver transcriptional network, including genes involved in bile acid metabolism. Transferring CR gut microbiota into mice fed with an obesogenic diet recapitulates the features of CR-related bile acid metabolism along with attenuated fatty liver. Conclusions These findings suggest that CR-induced microbiota shapes the hepatic epigenome followed by altered expression of genes responsible for bile acid metabolism.